The quaternary structure in solution of human complement subcomponent C1r2C1s2

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Abstract
Clr2Cls2 is a subcomponent of first component C1 of the complement cascade. Previously two distinct models for its structure have been described, in which Clr2Cls2 is either a linear rod-like assembly of the globular domains found in each of C1s and Clr, or these domains are arranged to form an asymmetric X-shaped structure. These two models were evaluated by using hydrodynamic simulations and neutron scattering. The data on Cls, Cls2 and Clr are readily represented by straight hydrodynamic cylinders, but not Clr2 or Clr2Cls2. Testis of the X-structure for Clr2 and Clr2 Cls2 successfully predicted the experimental sedimentation coefficients, thus supporting this mode. Neutron scattering analyses on C.hivin.1s and C.hivin.12 are consistent with a linear structure for C.hivin.1s, but not for Clr2. An X-shaped structure for Clr2 was found to give a good account of the neutral data at large scattering angles. The total length of the Cls and Clr monomers was determined as 17-20 nm, which is compatible with electron microsocpy. On the basis of the known sequences of Clr and Cls, this length is accounted for by a lienar arrangement of a serine-proteinase domain (length 4 nm), two short consensus repeat domains (2 .times. 4 nm), and a globular entity containing the I, II and domains (4-7 nm).